National Study of Deep Brain Stimulation for Depression Fails to Demonstrate Efficacy

According to new report in Biological Psychiatry

Share this:

Philadelphia, PA, July 28, 2015

Depression is a leading
cause of disability worldwide, and treatment-resistant symptoms of depression
have a terrible personal and societal cost. They can devastate lives, careers,
and families. Some severely ill patients may be unable to attend to even the
basic elements of self-care, while others attempt or complete suicide.

Because of the clinical
urgency, deep brain stimulation (DBS) treatments for depression have been developed
over the past 15 years. These treatments require surgery to make a small hole
in the skull through which an electrode is passed into a specific brain region.
Once positioned, a standard electrical stimulation procedure is initiated,
which is modeled after highly effective DBS treatments that are used for
Parkinson’s disease, essential tremor, and other neurologic conditions.

DBS does not damage healthy
brain tissue. It works by using electrical pulses to ‘block’ neural signals
from the targeted brain area that is the known or suspected source of the
symptoms.

A large number of relatively
small open-label studies have supported the effectiveness of various forms of
DBS for both depression and obsessive-compulsive disorder.

In the current issue of Biological Psychiatry, Dr. Darin Dougherty
and his colleagues report the results of the first large-scale, randomized,
sham-controlled trial of deep brain stimulation treatment for treatment-resistant
symptoms of depression. Thirty patients received active DBS or sham ‘placebo’ stimulation
for 16 weeks, targeted at the ventral capsule and ventral striatum, brain
regions implicated in reward and motivation. A two-year open-label continuation
phase followed.

This study, conducted at
five medical centers across the U.S. that collaborated on the project, failed
to find that DBS reduced depression symptoms better than sham stimulation.

“While initial open-label
trials of DBS at the ventral capsule/ventral striatum target were promising,
the results of this first controlled trial were negative,” explained Dougherty,
Director of Neurotherapeutics at Massachusetts General Hospital and Associate Professor
at Harvard Medical School.

Dr. Thomas Schlaepfer, an
expert on DBS treatment unaffiliated with this study, from Johns Hopkins
University and University Hospital Bonn in Germany, wrote a companion piece to
this article and commented, “On first sight, this might be seen as a crisis for
the whole field of neurostimulation therapies for depression… [but we] believe
that these are examples of failed studies
and not failed treatments.”

“This study raises serious
questions about the advisability of continuing to stimulate these reward
regions in the manner employed in this study,” said Dr. John Krystal, Editor of
Biological Psychiatry. “It is
critical to understand that this study is not a universal indictment of DBS as
a strategy for depression. It may turn out that stimulating other brain regions
or stimulating these regions in different ways could provide important
benefit.”

“Given the degree of
response that we have seen in some of the most treatment refractory patients, we
agree with Dr. Schlaepfer and Dr. Krystal. Alternative study designs will have
to be considered as we conduct future clinical trials in this critical area,” concluded
Dougherty.

Notes for editorsFull text of the article is available to credentialed journalists
upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu. Journalists
wishing to interview the authors may contact Darin Dougherty at +1 617 724 6300
or ddougherty@partners.org.

The
authors’ affiliations, and disclosures of financial and conflicts of interests
are available in the article.

John
H. Krystal, M.D., is Chairman of the Department of Psychiatry at the Yale
University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital,
and a research psychiatrist at the VA Connecticut Healthcare System. His
disclosures of financial and conflicts of interests are available here.

About
Biological PsychiatryBiological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote
excellence in scientific research and education in fields that investigate the nature,
causes, mechanisms and treatments of disorders of thought, emotion, or
behavior. In accord with this mission, this peer-reviewed, rapid-publication,
international journal publishes both basic and clinical contributions from all
disciplines and research areas relevant to the pathophysiology and treatment of
major psychiatric disorders.

The journal publishes novel results of original research
which represent an important new lead or significant impact on the field,
particularly those addressing genetic and environmental risk factors, neural
circuitry and neurochemistry, and important new therapeutic approaches. Reviews
and commentaries that focus on topics of current research and interest are also
encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in
the field of psychiatric neuroscience.
It is ranked 6th out of 140 Psychiatry titles and 10th
out of 252 Neurosciences titles in the Journal Citations Reports® published by
Thomson Reuters. The 2014 Impact Factor score for Biological Psychiatry
is 10.255.

About ElsevierElsevier is a global information analytics business that helps institutions and professionals advance healthcare, open science, and improve performance for the benefit of humanity. Elsevier provides digital solutions and tools in the areas of strategic research management, R&D performance, clinical decision support, and professional education; including ScienceDirect, Scopus, SciVal, ClinicalKey and Sherpath. Elsevier publishes over 2,500 digitized journals, including The Lancet and Cell, more than 35,000 e-book titles and many iconic reference works, including Gray's Anatomy. Elsevier is part of RELX Group, a global provider of information and analytics for professionals and business customers across industries. www.elsevier.com